CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1233 A Biodegradable Implant Releasing Low-Dose Islatravir Protects Macaques From Rectal SHIV Infection Jiyoung S. Kim 1 , Daniela Cruz 2 , Daniel Kim 3 , Archana Krovi 2 , Chasity Norton 2 , James Mitchell 1 , Rachel Wier 1 , Jeannette Dienhart 1 , Mackenzie Cottrell 4 , Seidu Inusah 1 , Gregory Gatto 2 , Walid Heneine 1 , Gerardo Garcia-Lerma 1 , Charles Dobard 1 , Leah Johnson 2 1 Centers for Disease Control and Prevention, Atlanta, GA, USA, 2 RTI Health Solutions, Research Triangle Park, NC, USA, 3 Emory University, Atlanta, GA, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Islatravir (ISL) is a potent nucleoside reverse transcriptase translocation inhibitor that was associated with lymphopenia in a dose dependent manner in clinical studies. We recently showed that treatment with high ISL doses in macaques also resulted in lymphopenia. Here, we evaluated preclinically a poly (ε-caprolactone) (PCL) implant designed to release low levels of ISL that are not predicted to cause lymphopenia. We investigated the safety and PK of ISL releasing implants and efficacy of low-dose ISL in protecting macaques against rectal SHIV infection. Methods: Biodegradable PCL implants (25mm length,300 µm wall-thickness) were loaded with approximately 42 mg of ISL and the in vitro release-rate (IVRR) was determined under sink conditions. A single ISL implant was placed in the arm of each rhesus macaque (n=6) using a trocar. ISL-TP levels in PBMCs were measured weekly by LC-MS/MS. Implant site reactions were graded using a modified Draize scale (range: 0-5). Macaques underwent a 7-week conditioning phase to achieve steady-state ISL-TP in PBMCs prior to rectal exposure to SHIV 162p3 twice-weekly during weeks 7-10 (up to 8 SHIV challenges). Macaques were monitored for SHIV infection during the challenge and follow-up period by RT-PCR. Infection outcomes were compared to 7 untreated animals. Results: The estimated IVRR of ISL was 135 µg/d. The median [range] ISL-TP levels in PBMCs during the conditioning phase was 136 fmol/106 cells [118-164]. During SHIV challenges, the ISL-TP level was 109 fmol/10 6 cells [76-141] or about 1 log10 lower than those seen in humans treated with 0.25 mg of once-daily oral ISL (1,140 fmol/10 6 cells)( Fig 1A ). ISL implants remained intact during the 5-month study period with no evidence of migration or implant-site reactions. The untreated controls were infected after a median of 1 SHIV challenge [range = 1-3]. In contrast, all ISL-treated macaques remained protected following repeated rectal SHIV challenges, resulting in an estimated efficacy of 100% ( Fig 1B ). Conclusions: ISL implants maintained structural integrity, provided sustained release of low-dose ISL, and showed no sign of local toxicities after 5 months. The ISL-TP levels in PBMCs remained below the clinical toxicity threshold and provided complete protection to macaques against rectal SHIV infection. Our study supports the development of a PCL implant that can deliver safe and effective ISL concentrations for ultra-long-acting HIV prevention. 1234 Qualitative Assessment of Acceptability and Preferences for Injectable and Oral PrEP in PURPOSE 1 Elizabeth (Liz) Montgomery 1 , Katherine Gill 2 , Timothy S. Hardwick 3 , Imogen Hawley 4 , Heeran Makkan 5 , Tara McClure 2 , Cecilia Milford 6 , Nzwakie Mosery 4 , Amukelani Nyathi 7 , Siyanda Tenza 3 , Alinda M. Nyamaizi 8 , Alexander Kintu 8 , Christoph Carter 8 , Moupali Das 7 , Thesla Palanee-Phillips, for the PURPOSE 1 Qualitative Study Team 1 Desmond Tutu HIV Foundation, Cape Town, South Africa, 2 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 3 RTI International, Oakland, CA, USA, 4 The Aurum Institute - Rustenburg Clinical Research Site, Rustenberg, South Africa, 5 FHI 360, Durham, NC, USA, 6 University of the Witwatersrand, Durban, South Africa, 7 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 8 Gilead Sciences, Inc, Foster City, CA, USA Background: PURPOSE 1 demonstrated 100% efficacy of twice-yearly injectable lenacapavir (LEN) for HIV pre-exposure prophylaxis (PrEP) in cisgender adolescent girls and young women. We conducted a nested qualitative sub-study exploring acceptability, preferences, and experiences with LEN and daily oral emtricitabine plus tenofovir alafenamide (F/TAF) or tenofovir disoproxil fumarate (F/TDF) for PrEP during the randomized blinded phase.

Methods: In-depth interviews (IDIs) were conducted at 5 geographically diverse South African trial sites, with: a) a randomly selected subset of participants aged 18–25 years at Weeks 13 and 52; b) purposively selected participants aged 16–17 years at Weeks 26 and 52; and c) participants aged 16–25 years who discontinued PrEP, were pregnant or breastfeeding (P/BF), or acquired HIV. IDIs were administered in English and/or local languages. Data were coded in Dedoose™, analyzed thematically, and summarized. Analyses were restricted to IDIs captured before PURPOSE 1 interim results. Results: Data from 108 participants (including: n=25 aged 16–17 years; n=16 discontinued; n=13 P/BF; n=8 acquired HIV) are described. LEN injections and both oral regimens were widely perceived as helpful and protective. Participants appreciated injections for their “once-off” 6-month activity and the potential implication of a worry-free HIV protection period, without taking daily tablets, barriers of concealing medication, or being judged for their use. Some participants reported injection-related concerns about “lumps” or pain that generally resolved within 1–2 days and was mitigated by analgesics. However, participants often felt that the benefits of duration of protection outweighed the often short-lived discomfort of injection receipt. Daily pill use was frequently reported to be difficult, “boring,” forgettable, and incompatible with lifestyles. Participants, particularly those aged 16–17 years, noted that injections suited their lifestyles, as they are “multitasking” and “juggling” along with “going out” and having “nice times,” making pill use inconvenient. Participants appreciated the smaller F/TAF (vs F/TDF) tablets and comparative ease in swallowing. Conclusions: PURPOSE 1 participants valued sustained protection from HIV, often preferred the lifestyle fit of a twice-yearly injectable vs daily oral PrEP, and accepted pain and injection-site reactions. These data suggest acceptability and preference for twice-yearly injections and/or F/TAF, reinforcing the value of product choice. 1235 Cost-Effectiveness of Community Pharmacy-Based HIV PrEP for Men Who Have Sex With Men in Atlanta Marita Zimmermann 1 , Anu Mishra 1 , Ryan Hansen 2 , Jacinda Tran 2 1 Bill & Melinda Gates Foundation, Seattle, WA, USA, 2 University of Washington, Seattle, WA, USA Background: The ongoing US HIV epidemic highlights the need for innovative strategies to promote pre-exposure prophylaxis (PrEP) uptake and reduce HIV incidence. Community pharmacy-based PrEP provides opportunity to expand access to this highly effective preventative therapy. Our study evaluated the potential health impacts, economic costs, and cost-effectiveness of community pharmacy-based PrEP for men who have sex with men (MSM) in the Atlanta metropolitan area, which has one of the highest burdens of HIV in the US. Methods: We adapted a calibrated and validated dynamic transmission compartmental model to simulate a hypothetical policy change permitting community pharmacists to initiate PrEP for eligible MSM in Atlanta. We compared the addition of community pharmacy-based PrEP to the status quo (traditional clinic-based), assuming 50% increase in PrEP uptake over 2 years. We conducted scenario analyses with varying assumptions related to PrEP adherence, persistence, and telehealth delivery based on early studies of pharmacy-based PrEP and other related, established pharmacy-based services. Using a healthcare sector perspective we projected the costs (2023 US dollars) and outcomes of (HIV cases averted, quality-adjusted life-years [QALY]) over a 50-year time horizon. One-way and probabilistic sensitivity analyses with 2,000 parameter sets were used to characterize model uncertainty. Results: We projected 34,670 new HIV cases and 89.5 million QALYs, at a cost of $423.8 billion, in the Atlanta metropolitan area under our status quo scenario. The addition of community pharmacy-based PrEP has the potential to reduce HIV incidence by 13.5%, increase QALYs by 0.2%, and decrease costs by 0.02% over the 50-year time horizon. Our scenario analyses consistently found pharmacy-based PrEP to result in improved health outcomes and either cost saving or cost-effective compared to the status quo. Conclusions: A policy permitting community pharmacies to provide PrEP services could lead to substantial clinical benefits and cost savings in Atlanta. However, additional research is needed to address challenges in scale-up, ensure financial sustainability, and realize the full potential of pharmacy-based PrEP interventions. Our study offers valuable insights for policymakers to improve access to HIV PrEP and work towards ending the HIV epidemic in the US.

Poster Abstracts

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